Deep learning segmentation of peri-sinus structures from structural magnetic resonance imaging: validation and normative ranges across the adult lifespan.

BACKGROUND: Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid (CSF) egress and neuroimmune surveillance. Neurofluid circulation dysfunction may manifest as morphological changes in these structures, however, automated quantification of these structures is not possible and rather characterization often requires exogenous contrast agents and manual delineation. METHODS: We propose a deep learning architecture to automatically delineate the peri-sinus space (e.g., PSD and intravenous AG structures) using two cascaded 3D fully convolutional neural networks applied to submillimeter 3D T2-weighted non-contrasted MRI images, which can be routinely acquired on all major MRI scanner vendors. The method was evaluated through comparison with gold-standard manual tracing from a neuroradiologist (n = 80; age range = 11-83 years) and subsequently applied in healthy participants (n = 1,872; age range = 5-100 years), using data from the Human Connectome Project, to provide exemplar metrics across the lifespan. Dice-Sørensen and a generalized linear model was used to assess PSD and AG changes across the human lifespan using quadratic restricted splines, incorporating age and sex as covariates. RESULTS: Findings demonstrate that the PSD and AG volumes can be segmented using T2-weighted MRI with a Dice-Sørensen coefficient and accuracy of 80.7 and 74.6, respectively. Across the lifespan, we observed that total PSD volume increases with age with a linear interaction of gender and age equal to 0.9 cm3 per year (p < 0.001). Similar trends were observed in the frontal and parietal, but not occipital, PSD. An increase in AG volume was observed in the third to sixth decades of life, with a linear effect of age equal to 0.64 mm3 per year (p < 0.001) for total AG volume and 0.54 mm3 (p < 0.001) for maximum AG volume. CONCLUSIONS: A tool that can be applied to quantify PSD and AG volumes from commonly acquired T2-weighted MRI scans is reported and exemplar volumetric ranges of these structures are provided, which should provide an exemplar for studies of neurofluid circulation dysfunction. Software and training data are made freely available online ( https://github.com/hettk/spesis ).

Resident operative time as an independent predictor of early post-operative cataract surgery outcomes and supervising attending surgeon impact: a retrospective case series.

BACKGROUND: The authors sought to determine if resident operative time in cataract extraction and intraocular lens insertion (CE/IOL) affects early visual outcomes and post-operative recovery. They further sought to investigate if attending surgeons can reduce resident operative time. METHODS: This retrospective, chart-review, case series at single Veterans Affairs Hospital (VA Tennessee Valley Healthcare System) studied resident cataract surgeries between March 1, 2018 and March 31, 2020. Following power analysis, 420 eyes of 400 patients from all resident cataract surgeries were included. Eyes with attending as primary surgeon, laser-assisted cataract surgery, or concurrent secondary procedures were excluded. Linear mixed effect models were used to study the association between operative time and visual outcomes while adjusting for covariates including cumulative dissipated energy, preoperative factors, and intraoperative complications. RESULTS: Longer operative time was statistically associated with worse post-operative-day 1 (POD1) pinhole visual acuity (PH-VA) adjusting for cumulative dissipated energy and other operative factors (p = 0.049). Although resident physicians were the primary surgeons, the operative times were different between the ten supervising attending surgeons in the study (p < 0.001). CONCLUSION: The results suggest that increased resident operative time is a significant, independent risk factor for decreased POD1 PH-VA. Increased resident operative time is not associated with worsened long term visual outcomes. Attending surgeons may be able to reduce resident operative time, which is associated with improved early visual outcomes.

Shedding light on eye disease in obesity: A review.

Obesity is known to be associated with numerous ocular manifestations, including but not limited to, diabetic retinopathy (DR), age-related macular degeneration (AMD), cataracts, glaucoma, and dry eye disease. This review aims to provide an overview of the ophthalmological findings in obesity. A literature search was conducted using PubMed and Cochrane databases for studies describing randomized clinical trials, meta-analyses, systematic reviews, and observational studies published from 1 January 2017 to 1 April 2023. The search terms used included relevant keywords such as 'obesity', 'body mass index', 'waist-to-hip ratio', 'bariatric', 'ophthalmology', 'eye disease', 'myopia', 'retinopathy', 'glaucoma', and 'cataract'. This literature search was performed on 1 April 2023. Obesity is associated with increased risk of developing DR, a sight-threatening complication of diabetes mellitus. Similarly, obesity has been shown to increase risk of AMD, cataracts, glaucoma, and ocular surface disease. Multiple mechanisms linking obesity to ophthalmic disease have been proposed. Adipose tissue produces various inflammatory cytokines that can affect ocular tissues, leading to disease progression. Additionally, obesity is associated with systemic metabolic changes that can influence ocular health. Bariatric surgery has been shown to be protective against development of ophthalmic disease. Obesity is a significant risk factor for several ophthalmological diseases. Healthcare providers should encourage weight loss in patients with overweight or obesity to prevent or delay the onset of ocular complications. Further research is needed to better understand the underlying mechanisms of this association, and to identify effective strategies for preventing or managing ophthalmic disease in patients with obesity.

Effects of Cost Sharing on Ophthalmic Care Utilization in the Affordable Care Act Marketplace.

PURPOSE: To determine the distribution and quantity of ophthalmic care consumed on Affordable Care Act (ACA) plans, the demographics of the population utilizing these services, and the relationship between ACA insurance coverage plan tier, cost sharing, and total cost of ophthalmic care consumed. METHODS: This cross-sectional study analyzed ACA individual and small group market claims data from the Wakely Affordable Care Act (WACA) 2018 dataset, which contains detailed claims, enrollment, and premium data from Edge Servers for 3.9 million individual and small group market lives. We identified all enrollees with ophthalmology-specific billing, procedure, and national drug codes. We then analyzed the claims by plan type and calculated the total cost and out-of-pocket (OOP) cost. RESULTS: Among 3.9 million enrollees in the WACA 2018 dataset, 538,169 (13.7%) had claims related to ophthalmology procedures, medications, and/or diagnoses. A total of $203 million was generated in ophthalmology-related claims, with $54 million in general services, $42 million in medications, $20 million in diagnostics and imaging, and $86 million in procedures. Average annual OOP costs were $116 per member, or 30.9% of the total cost, and were lowest for members with platinum plans (16% OOP) and income-driven cost sharing reduction (ICSR) subsidies (17% OOP). Despite stable ocular disease distribution across plan types, beneficiaries with silver ICSR subsidies consumed more total care than any other plan, higher than platinum plan enrollees and almost 1.5× the cost of bronze plan enrollees. CONCLUSIONS: Ophthalmic care for enrollees on ACA plans generated substantial costs in 2018. Plans with higher OOP cost sharing may result in lower utilization of ophthalmic care.

Modeling the Environmental and Financial Impact of Multi-dose vs. Single-dose Iodinated Contrast Media Packaging and Delivery Systems.

RATIONALE AND OBJECTIVES: Iodinated contrast media (ICM) is used in computed tomography (CT) imaging to better visualize pathophysiology. ICM is commonly sold in "single-dose" bottles that require any unused volume to be discarded. Multi-dose bottles have been developed as an alternative packaging method. The objective of this study was to compare ICM waste, plastic waste, and the associated financial costs for both the single-dose and multi-dose ICM delivery systems. METHODS: Institutional data was used to estimate the average ICM administered per CT scan, average ICM wasted per CT scan, and the total ICM volume wasted annually. Waste estimates for the multi-dose bottles were generated by applying the average ICM administered per CT scan to the larger, multi-dose bottle volumes. Single-dose bottles, multi-dose bottles and injection syringes were weighed and used to calculate plastic waste generated by both packaging methods. Financial analysis was performed to compare the cost of supplies for single-dose and multi-dose ICM delivery systems. RESULTS: We found that 100 mL single-dose ICM bottles waste an average of 19.7 mL per CT scan, representing over 964 L of ICM wasted per year. The multi-dose ICM delivery system was projected to decrease pharmaceutical waste by at least 73% and reduce plastic waste by approximately 93%. We also estimate $494,000 in annual savings using the multi-dose ICM delivery method at our institution. CONCLUSION: Multi-dose ICM packaging can help conserve ICM, an important pharmaceutical that was only recently severely affected supply chain disruptions. The multi-dose delivery system can also reduce plastic waste and generate substantial financial savings to offset capital investment.

Evaluation of Two-Dimensional (2D) versus Three-Dimensional (3D) Video Tutorials in Cataract Surgery for New Trainees.

Purpose Microscopic ophthalmic surgery requires an understanding of three-dimensional (3D) spaces within the eye. Recently, there has been an increase in 3D video training tools in health care. Studies have evaluated the efficacy of 3D tutorials in general surgery, but little has been published within ophthalmology. We present a randomized study evaluating differences in surgically naïve trainees after watching either a 2D or 3D phacoemulsification tutorial. Design This was a double-blind, randomized study. A group of third and fourth year medical students at our institution were randomized with stratified randomization based on prior surgical courses to control for differences in baseline surgical skill. The two study arms were watching 2D or 3D instructional videos on phacoemulsification (Richard Mackool). Methods Participants received a preliminary survey and participated in an hour-long microscopic surgery session. During the session, participants performed tasks evaluating baseline microscopic spatial awareness and surgical skill. The students were then instructed to watch either a 2D or 3D video on phacoemulsification based on their randomized study arm. During the postintervention session, participants performed the biplanar incision and capsulorhexis steps of cataract surgery discussed in the video on model eyes. Students were evaluated on speed and overall capsulorhexis quality. Results Thirty-one students qualified for the study and completed the microscopic surgery session. Students in both groups had similar baseline speed and quality of preintervention microscopic tasks ( p > 0.05 for all tasks). Postintervention, students randomized to the 3D video performed significantly faster than the 2D group for biplanar incision (11.1 ± 5.5 s vs. 20.7 ± 10.5 s, p = 0.001). There were no statistically significant differences found between the groups in capsulorhexis timing ( p = 0.12) or quality score ( p = 0.60). Conclusions 3D video surgical training tutorials may improve speed of certain steps of cataract surgery for surgically naïve ophthalmology trainees. Given the limited sample size of this study, further investigation of their effectiveness is warranted.

Parasagittal dural space and cerebrospinal fluid (CSF) flow across the lifespan in healthy adults.

BACKGROUND: Recent studies have suggested alternative cerebrospinal fluid (CSF) clearance pathways for brain parenchymal metabolic waste products. One fundamental but relatively under-explored component of these pathways is the anatomic region surrounding the superior sagittal sinus, which has been shown to have relevance to trans-arachnoid molecular passage. This so-called parasagittal dural (PSD) space may play a physiologically significant role as a distal intracranial component of the human glymphatic circuit, yet fundamental gaps persist in our knowledge of how this space changes with normal aging and intracranial bulk fluid transport. METHODS: We re-parameterized MRI methods to assess CSF circulation in humans using high resolution imaging of the PSD space and phase contrast measures of flow through the cerebral aqueduct to test the hypotheses that volumetric measures of PSD space (1) are directly related to CSF flow (mL/s) through the cerebral aqueduct, and (2) increase with age. Multi-modal 3-Tesla MRI was applied in healthy participants (n = 62; age range = 20-83 years) across the adult lifespan whereby phase contrast assessments of CSF flow through the aqueduct were paired with non-contrasted T1-weighted and T2-weighted MRI for PSD volumetry. PSD volume was extracted using a recently validated neural networks algorithm. Non-parametric regression models were applied to evaluate how PSD volume related to tissue volume and age cross-sectionally, and separately how PSD volume related to CSF flow (significance criteria: two-sided p < 0.05). RESULTS: A significant PSD volume enlargement in relation to normal aging (p < 0.001, Spearman's-[Formula: see text] = 0.6), CSF volume (p < 0.001, Spearman's-[Formula: see text] = 0.6) and maximum CSF flow through the aqueduct of Sylvius (anterograde and retrograde, p < 0.001) were observed. The elevation in PSD volume was not significantly related to gray or white matter tissue volumes. Findings are consistent with PSD volume increasing with age and bulk CSF flow. CONCLUSIONS: Findings highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Additionally, findings demonstrate that PSD volume increases with age and relates to CSF volume and bi-directional flow. Values reported should provide useful normative ranges for how PSD volume adjusts with age, which will serve as a necessary pre-requisite for comparisons to persons with neurodegenerative disorders.

Risk of Infectious Endophthalmitis From a Resident-Performed Intravitreal Injection.

PURPOSE: This work assesses the safety of resident-performed intravitreal injections by comparing the incidence of postinjection endophthalmitis associated with residents vs surgical retina attendings. METHODS: In this retrospective noninferiority cohort study, the Current Procedural Technology code for an intravitreal injection was used to identify patients from July 1, 2015, to October 31, 2018, at a single-center Veterans Affairs hospital where patients receive intravitreal injections from attending vitreoretinal surgeons and residents. The medical record for each injection was reviewed for the training level of the proceduralist, indication, medication, and laterality. The main outcome was the incidence of postinjection endophthalmitis occurring within 30 days of an intravitreal injection, which was confirmed by at least 2 medical-record reviewers. RESULTS: In this cohort of 593 patients, most were male (97.0%), and the average age was 70.3 years (±10.8 years). Of the 6934 injections given, 3877 (55.9%) were performed by residents and 3057 (44.1%) by attendings. Of the 5 cases of endophthalmitis identified, 3 were associated with a resident-performed injection in his or her fourth year of postgraduate training. The difference (0.012%; 95% CI, -0.168% to 0.169%) in the incidence of postinjection endophthalmitis between residents (0.077%) and attendings (0.065%) did not cross the predetermined noninferiority limit (0.200%). CONCLUSIONS: At our teaching clinic, resident-performed injections were not associated with an elevated risk of endophthalmitis when compared with attending-performed injections. Under varying levels of supervision, residents appeared to demonstrate appropriate sterile injection technique.

The role of galactomannan Aspergillus antigen in diagnosing acute invasive fungal sinusitis.

BACKGROUND: Pathologic diagnosis remains the gold standard for final diagnosis of acute invasive fungal sinusitis (AIFS); however, other less invasive tests could suggest the presence of AIFS in at-risk populations where early diagnosis is crucial. Serum galactomannan Aspergillus antigen has been shown to correlate with a diagnosis of invasive pulmonary aspergillosis; however, it has not adequately been evaluated in regard to AIFS. The objective of this study is to evaluate the statistical relevance of galactomannan in predicting diagnosis of AIFS. METHODS: This study was a retrospective review of pathologic records using Co-Path from 2006 to 2017, incorporating 2 separate searches with designated criteria identifying patients who received pathologic evaluation for invasive fungal sinusitis. Electronic medical records were subsequently reviewed. After exclusions isolating at-risk populations and removing duplications, 78 cases were reviewed using the indicated search criteria. Of these, 38 met further criteria of having had both pathologic evaluation and galactomannan analysis. Statistical variables were assessed, as well as all-cause mortality. Peak and closest galactomannan levels were evaluated. RESULTS: Overall, galactomannan had a sensitivity of 44.8% (95% confidence interval [CI], 26.5% to 64.3%), specificity of 100% (95% CI, 66.4% to 100%), positive predictive value of 100% (95% CI, 74.3% to 100%), and negative predictive value of 36% (95% CI, 18.0% to 57.5%). No significant association was observed in galactomannan status and mortality in this patient population. CONCLUSION: Positive serum galactomannan can be an indication of AIFS in patients with a high clinical suspicion. In our study, a positive galactomannan always correlated with a positive pathologic diagnosis. However, given its low sensitivity, one must use caution in relying on galactomannan as a screening tool in diagnosis of AIFS.

An Embryonic and Induced Pluripotent Stem Cell Model for Ovarian Granulosa Cell Development and Steroidogenesis.

Embryoid bodies (EBs) can serve as a system for evaluating pluripotency, cellular differentiation, and tissue morphogenesis. In this study, we use EBs derived from mouse embryonic stem cells (mESCs) and human amniocyte-derived induced pluripotent stem cells (hAdiPSCs) as a model for ovarian granulosa cell (GC) development and steroidogenic cell commitment. We demonstrated that spontaneously differentiated murine EBs (mEBs) and human EBs (hEBs) displayed ovarian GC markers, such as aromatase (CYP19A1), FOXL2, AMHR2, FSHR, and GJA1. Comparative microarray analysis identified both shared and unique gene expression between mEBs and the maturing mouse ovary. Gene sets related to gonadogenesis, lipid metabolism, and ovarian development were significantly overrepresented in EBs. Of the 29 genes, 15 that were differentially regulated in steroidogenic mEBs displayed temporal expression changes between embryonic, postnatal, and mature ovarian tissues by polymerase chain reaction. Importantly, both mEBs and hEBs were capable of gonadotropin-responsive estradiol (E2) synthesis in vitro (217-759 pg/mL). Live fluorescence-activated cell sorting-sorted AMHR2+ granulosa-like cells from mEBs continued to produce E2 after purification (15.3 pg/mL) and secreted significantly more E2 than AMHR2- cells (8.6 pg/mL, P < .05). We conclude that spontaneously differentiated EBs of both mESC and hAdiPSC origin can serve as a biologically relevant model for ovarian GC differentiation and steroidogenic cell commitment. These cells should be further investigated for therapeutic uses, such as stem cell-based hormone replacement therapy and in vitro maturation of oocytes.

Cardiac magnetic resonance in cardiac angiosarcoma.

BACKGROUND: While echocardiography is effective for initial identification of anatomic location, magnetic resonance imaging (MRI) is a more advantageous modality for delineating tumor expanse, spread, and blood supply preoperatively. Emerging patterns may even help generate a specific diagnosis prior to biopsy and histopathology. CASE PRESENTATION: Our case of a 67-year-old male referred for cardiac magnetic resonance to further evaluate a cardiac mass highlights the sophisticated level of data which can be collected. Our case highlights the perfusion related findings associated with cardiac angiosarcoma. CONCLUSION: In this case, we present the diagnosis of right atrial cardiac angiosarcoma by multiple imaging modalities including MRI and subsequent angiography, allowing for prompt surgical intervention and initiation of adjuvant therapy that resulted in a survival time of 19 months.

Hereditary leiomyomatosis and renal cell cancer: Cutaneous lesions & atypical fibroids.

OBJECTIVE: To report a diagnosis of hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome following initial presentation with multiple cutaneous lesions. DESIGN: Case report. DESIGN CLASSIFICATION: N/A. SETTING: Academic tertiary care center. PATIENTS: 27-year-old nulligravid woman who presented with multiple red-brown lesions on her skin found to have cutaneous and uterine leiomyoma. INTERVENTIONS: Biopsy of cutaneous lesions and fertility sparing robot-assisted laparoscopic myomectomy (RALM). MAIN OUTCOME MEASURESS: Histological assessment of uterine leiomyoma. RESULTSS: Pathologic examination of uterine leiomyoma revealed diffuse atypia and fumarate hydratase loss phenotype concerning for genetic syndrome. Follow-up DNA sequencing via Sanger sequencing confirmed a pathogenetic R2333H mutation consistent with HLRCC. CONCLUSIONS: Consideration of HLRCC on differential diagnosis when patients present with cutaneous nodules and atypical or early onset uterine leiomyoma provides opportunity for early surveillance, family member testing, and more thoughtful surgical planning. PRECIS: 27-year-old woman with multiple cutaneous lesions is found to have uterine leiomyomas and undergoes robotic myomectomy. Genetic testing of uterine leiomyomas reveals mutation in fumarate hydratase, etiologic in hereditary leiomyomatosis and renal cell cancer (HLRCC).

Socioeconomic Disparities in Cataract Prevalence, Characteristics, and Management.

PURPOSE: To review the current literature on socioeconomic disparities relationship with cataract prevalence, characteristics, and management. SUMMARY: Cataracts are an important cause of preventable visual impairment in both the developing and industrialized world. Cataract surgery is a highly effective operation with an excellent risk profile. Furthermore, cataract surgery has been shown to have significant positive functional, social, and economic implications for patients. Several medical conditions have been shown to have correlation with socioeconomic factors and cataract is among several forms of visual impairment that demonstrate this relationship. Disparities in prevalence, clinical characteristics, and management are documented in the ophthalmic literature. A better understanding of these socioeconomic factors and their clinical relevance is critical to alleviating the burden of cataract-related visual impairment in an aging population.

Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells.

To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs), we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs) using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs) was verified by demonstrating embryonic stem cell (ESC) antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs) and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs) revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2) than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4) and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha) as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1) more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.

Functional maintenance of differentiated embryoid bodies in microfluidic systems: a platform for personalized medicine.

Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin ß-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30-120 pg/ml and 150-450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine.

Pax6- and Six3-mediated induction of lens cell fate in mouse and human ES cells.

Embryonic stem (ES) cells provide a potentially useful in vitro model for the study of in vivo tissue differentiation. We used mouse and human ES cells to investigate whether the lens regulatory genes Pax6 and Six3 could induce lens cell fate in vitro. To help assess the onset of lens differentiation, we derived a new mES cell line (Pax6-GFP mES) that expresses a GFP reporter under the control of the Pax6 P0 promoter and lens ectoderm enhancer. Pax6 or Six3 expression vectors were introduced into mES or hES cells by transfection or lentiviral infection and the differentiating ES cells analyzed for lens marker expression. Transfection of mES cells with Pax6 or Six3 but not with other genes induced the expression of lens cell markers and up-regulated GFP reporter expression in Pax6-GFP mES cells by 3 days post-transfection. By 7 days post-transfection, mES cell cultures exhibited a>10-fold increase over controls in the number of colonies expressing γA-crystallin, a lens fiber cell differentiation marker. RT-PCR and immunostaining revealed induction of additional lens epithelial or fiber cell differentiation markers including Foxe3, Prox1, α- and ß-crystallins, and Tdrd7. Moreover, γA-crystallin- or Prox1-expressing lentoid bodies formed by 30 days in culture. In hES cells, Pax6 or Six3 lentiviral vectors also induced lens marker expression. mES cells that express lens markers reside close to but are distinct from the Pax6 or Six3 transduced cells, suggesting that the latter induce nearby undifferentiated ES cells to adopt a lens fate by non-cell autonomous mechanisms. In sum, we describe a novel mES cell GFP reporter line that is useful for monitoring induction of lens fate, and demonstrate that Pax6 or Six3 is sufficient to induce ES cells to adopt a lens fate, potentially via non-cell autonomous mechanisms. These findings should facilitate investigations of lens development.

Surgical management of massive labial edema in a gravid preeclamptic diabetic.

Background. Massive labial edema is a rare complication during pregnancy that can jeopardize vaginal delivery, as well as leading to maternal and fetal morbidity. It can be related to systemic pathologies, but has been commonly associated with preeclampsia and diabetes. This increased and sometimes longstanding pressure may result in a "labial compartment syndrome" leading to microvascular damage and tissue necrosis if not resolved in a timely fashion. Case. Massive labial edema was treated first conservatively and then surgically in a gravid diabetic patient with severe preeclampsia. Immediately after Cesarean section, the labial compartment syndrome was relieved surgically and resolved rapidly. Conclusion. When conservative attempts at management of labial edema fail, or rapid resolution is critical to maternal and fetal outcome, surgical alternatives should be considered.